Document Detail


Effective Gene Delivery Using Stimulus-Responsive Catiomer Designed with Redox-Sensitive Disulfide and Acid-Labile Imine Linkers.
MedLine Citation:
PMID:  22443494     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
A dual stimulus-responsive mPEG-SS-PLL(15)-glutaraldehyde star (mPEG-SS-PLL(15)-star) catiomer is developed and biologically evaluated. The catiomer system combines redox-sensitive removal of an external PEG shell with acid-induced escape from the endosomal compartment. The design rationale for PEG shell removal is to augment intracellular uptake of mPEG-SS-PLL(15)-star/DNA complexes in the presence of tumor-relevant glutathione (GSH) concentration, while the acid-induced dissociation is to accelerate the release of genetic payload following successful internalization into targeted cells. Size alterations of complexes in the presence of 10 mM GSH suggest stimulus-induced shedding of external PEG layers under redox conditions that intracellularly present in the tumor microenvironment. Dynamic laser light scattering experiments under endosomal pH conditions show rapid destabilization of mPEG-SS-PLL(15)-star/DNA complexes that is followed by facilitating efficient release of encapsulated DNA, as demonstrated by agarose gel electrophoresis. Biological efficacy assessment using pEGFP-C1 plasmid DNA encoding green fluorescence protein and pGL-3 plasmid DNA encoding luciferase as reporter genes indicate comparable transfection efficiency of 293T cells of the catiomer with a conventional polyethyleneimine (bPEI-25k)-based gene delivery system. These experimental results show that mPEG-SS-PLL(15)-star represents a promising design for future nonviral gene delivery applications with high DNA binding ability, low cytotoxicity, and high transfection efficiency.
Authors:
Xiaojun Cai; Chunyan Dong; Haiqing Dong; Gangmin Wang; Giovanni M Pauletti; Xiaojing Pan; Huiyun Wen; Isaac Mehl; Yongyong Li; Donglu Shi
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-26
Journal Detail:
Title:  Biomacromolecules     Volume:  -     ISSN:  1526-4602     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-3-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100892849     Medline TA:  Biomacromolecules     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
The Institute for Advanced Materials and Nano Biomedicine, School of Medicine, ‡Department of Oncology, Shanghai East Hospital, and §School of Life Science and Technology, Tongji University , Shanghai 200092, China.
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